A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells

Abstract Harnessing complement-mediated cytotoxicity by therapeutic antibodies has been limited because of dependency on size and density of antigen, structural constraints resulting from orientation of antibody binding, and blockade of complement activation by inhibitors expressed on target cells....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jonathan W. Cruz, Ermelinda Damko, Bhavika Modi, Naxin Tu, Karoline Meagher, Vera Voronina, Hans Gartner, George Ehrlich, Ashique Rafique, Robert Babb, Priya Aneja, Terra B. Potocky, Amanda D’ Orvilliers, Alida Coppi, Sook Yen E, Haibo Qiu, Courtney M. Williams, Brandy L. Bennett, Gang Chen, Lynn Macdonald, William Olson, John C. Lin, Neil Stahl, Andrew J. Murphy, Christos A. Kyratsous, Brinda C. Prasad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1c56187022f4047924380652a772499
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a1c56187022f4047924380652a772499
record_format	dspace
spelling	oai:doaj.org-article:a1c56187022f4047924380652a7724992021-12-02T15:08:58ZA novel bispecific antibody platform to direct complement activity for efficient lysis of target cells10.1038/s41598-019-48461-12045-2322https://doaj.org/article/a1c56187022f4047924380652a7724992019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48461-1https://doaj.org/toc/2045-2322Abstract Harnessing complement-mediated cytotoxicity by therapeutic antibodies has been limited because of dependency on size and density of antigen, structural constraints resulting from orientation of antibody binding, and blockade of complement activation by inhibitors expressed on target cells. We developed a modular bispecific antibody platform that directs the complement-initiating protein C1q to target cells, increases local complement deposition and induces cytotoxicity against target antigens with a wide-range of expression. The broad utility of this approach to eliminate both prokaryotic and eukaryotic cells was demonstrated by pairing a unique C1q-recruiting arm with multiple targeting arms specific for Staphylococcus aureus, Pseudomonas aeruginosa, B-cells and T-cells, indicating applicability for diverse indications ranging from infectious diseases to cancer. Generation of C1q humanized mice allowed for demonstration of the efficacy of this approach to clear disease-inducing cells in vivo. In summary, we present a novel, broadly applicable, and versatile therapeutic modality for targeted cell depletion.Jonathan W. CruzErmelinda DamkoBhavika ModiNaxin TuKaroline MeagherVera VoroninaHans GartnerGeorge EhrlichAshique RafiqueRobert BabbPriya AnejaTerra B. PotockyAmanda D’ OrvilliersAlida CoppiSook Yen EHaibo QiuCourtney M. WilliamsBrandy L. BennettGang ChenLynn MacdonaldWilliam OlsonJohn C. LinNeil StahlAndrew J. MurphyChristos A. KyratsousBrinda C. PrasadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-16 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan W. Cruz Ermelinda Damko Bhavika Modi Naxin Tu Karoline Meagher Vera Voronina Hans Gartner George Ehrlich Ashique Rafique Robert Babb Priya Aneja Terra B. Potocky Amanda D’ Orvilliers Alida Coppi Sook Yen E Haibo Qiu Courtney M. Williams Brandy L. Bennett Gang Chen Lynn Macdonald William Olson John C. Lin Neil Stahl Andrew J. Murphy Christos A. Kyratsous Brinda C. Prasad A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
description	Abstract Harnessing complement-mediated cytotoxicity by therapeutic antibodies has been limited because of dependency on size and density of antigen, structural constraints resulting from orientation of antibody binding, and blockade of complement activation by inhibitors expressed on target cells. We developed a modular bispecific antibody platform that directs the complement-initiating protein C1q to target cells, increases local complement deposition and induces cytotoxicity against target antigens with a wide-range of expression. The broad utility of this approach to eliminate both prokaryotic and eukaryotic cells was demonstrated by pairing a unique C1q-recruiting arm with multiple targeting arms specific for Staphylococcus aureus, Pseudomonas aeruginosa, B-cells and T-cells, indicating applicability for diverse indications ranging from infectious diseases to cancer. Generation of C1q humanized mice allowed for demonstration of the efficacy of this approach to clear disease-inducing cells in vivo. In summary, we present a novel, broadly applicable, and versatile therapeutic modality for targeted cell depletion.
format	article
author	Jonathan W. Cruz Ermelinda Damko Bhavika Modi Naxin Tu Karoline Meagher Vera Voronina Hans Gartner George Ehrlich Ashique Rafique Robert Babb Priya Aneja Terra B. Potocky Amanda D’ Orvilliers Alida Coppi Sook Yen E Haibo Qiu Courtney M. Williams Brandy L. Bennett Gang Chen Lynn Macdonald William Olson John C. Lin Neil Stahl Andrew J. Murphy Christos A. Kyratsous Brinda C. Prasad
author_facet	Jonathan W. Cruz Ermelinda Damko Bhavika Modi Naxin Tu Karoline Meagher Vera Voronina Hans Gartner George Ehrlich Ashique Rafique Robert Babb Priya Aneja Terra B. Potocky Amanda D’ Orvilliers Alida Coppi Sook Yen E Haibo Qiu Courtney M. Williams Brandy L. Bennett Gang Chen Lynn Macdonald William Olson John C. Lin Neil Stahl Andrew J. Murphy Christos A. Kyratsous Brinda C. Prasad
author_sort	Jonathan W. Cruz
title	A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
title_short	A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
title_full	A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
title_fullStr	A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
title_full_unstemmed	A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
title_sort	novel bispecific antibody platform to direct complement activity for efficient lysis of target cells
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/a1c56187022f4047924380652a772499
work_keys_str_mv	AT jonathanwcruz anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT ermelindadamko anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT bhavikamodi anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT naxintu anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT karolinemeagher anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT veravoronina anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT hansgartner anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT georgeehrlich anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT ashiquerafique anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT robertbabb anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT priyaaneja anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT terrabpotocky anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT amandadorvilliers anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT alidacoppi anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT sookyene anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT haiboqiu anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT courtneymwilliams anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT brandylbennett anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT gangchen anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT lynnmacdonald anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT williamolson anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT johnclin anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT neilstahl anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT andrewjmurphy anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT christosakyratsous anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT brindacprasad anovelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT jonathanwcruz novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT ermelindadamko novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT bhavikamodi novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT naxintu novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT karolinemeagher novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT veravoronina novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT hansgartner novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT georgeehrlich novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT ashiquerafique novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT robertbabb novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT priyaaneja novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT terrabpotocky novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT amandadorvilliers novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT alidacoppi novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT sookyene novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT haiboqiu novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT courtneymwilliams novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT brandylbennett novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT gangchen novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT lynnmacdonald novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT williamolson novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT johnclin novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT neilstahl novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT andrewjmurphy novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT christosakyratsous novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells AT brindacprasad novelbispecificantibodyplatformtodirectcomplementactivityforefficientlysisoftargetcells
_version_	1718387955616186368

A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells

Ejemplares similares